New Research Strategies Proposed for Developing Antibiotics

There’s a mounting campaign to encourage biopharmaceutical companies to develop new therapies to treat drug-resistant infections by offering a range of flexible regulatory policies plus financial incentives to make exploration and clinical research more attractive. The spreading Ebola outbreak has further dramatized the critical need for new drugs and biologics to combat public health crises caused by infectious disease, clearly illustrating the importance of streamlined development approaches and added financial support for R&D on medical products with uncertain commercial value.

A sign of progress is Food and Drug Administration approval in recent months of three new antibiotics to treat patients with acute bacterial skin infections, including methicillin-resistant strains (MRSA). Product development was encouraged by additional guidance from FDA, plus collaboration with the Biomarkers Consortium of the Foundation of the National Institutes of Health and others in designing scientifically sound studies, commented Janet Woodcock, Director of the Center for Drug Evaluation and Research (CDER).

Woodcock also noted at a September hearing by the House Energy & Commerce Committee 21st Century Cures initiative that in the last two years FDA has promoted antibiotic R&D by issuing 11 relevant guidance documents. An FDA public workshop in July on strategies for conducting clinical trials for antibacterials discussed design of common protocols, establishing common control groups, addressing statistical analysis issues, setting appropriate study endpoints, and sharing data and data standards across trials.

Seeking new approaches

FDA gives credit for spurring more interest in antibiotic development to the additional five years of marketing exclusivity provided by the Generating Antibiotics Incentives Now (GAIN) Act of 2012. The exclusivity applies to new drugs designated by FDA as Qualified Infectious Disease Products (QIDPs), which FDA has granted so far to 39 antibiotics under development. But biopharma companies say the added exclusivity has limited value and that further legislative action is necessary.

Some proposals for accelerating clinical trials on new antibiotics have come from the President’s Council of Advisors on Science and Technology (PCAST). The panel issued a report in September outlining strategies to accelerate clinical trials on new antibiotics, such as an FDA Special Medical Use pathway that streamlines clinical testing for therapies needed by specific patients infected with antibiotic-resistant bacteria. Similarly, a Congressional proposal would establish a Limited Population Antibacterial Drug (LPAD) program that authorizes FDA to approve antibiotics based on more limited clinical trial data. Preapproval studies would require fewer patients, while post-approval assessment would be more extensive to further assess uncertainty of risks and benefits.

PCAST also calls for allotting $25 million a year to fund a clinical trials infrastructure that would implement common protocols, form partnerships to fund late stage trials, and facilitate fast enrollment of patients with an antibiotic-resistant infection. These streamlined clinical research approaches would benefit, moreover, from new diagnostics able to identify those patients likely to respond and require clear instructions to the medical community on the importance of limited use of new products to prevent resistance.

To reward sponsors with later stage projects, PCAST proposes an $800 million public-private Antibiotic Incentive Fund to finance advanced market commitments and milestone payments. A related idea is to provide developers of new antibiotics with a “tradable voucher” that grants a short extension to the patent life of any drug, and thus could be sold by a small company to a manufacturer looking to extend protection for an existing blockbuster.

Another tactic backed by some members of Congress is to encourage hospital use of new, more costly antibiotics through added government payments and revised reimbursement policies that permit separate payment for more effective antibiotics outside the fixed “bundled” rate set for inpatient care. Additional tax credits and government subsidies, plus milestone payments for completing various clinical trials, were proposed at the E&C hearing by Kenneth Hills, Chief Executive of biotech antibiotic developer Achaeogen, to further encourage innovation.

These and other proposals may be included in a legislative package slated to be introduced by E&C leaders at the beginning of the next legislative session in January. And in February, an Obama administration interagency task force headed by officials from the Departments of Health and Human Services, Agriculture and Defense is scheduled to issue a detailed plan for implementing the White House National Strategy to Combat Antibiotic-Resistant Bacteria. That initiative was launched in September with the aim of preventing outbreaks and encouraging development of next-generation antibacterial drugs, diagnostics, vaccines and other therapeutics to combat infectious disease. An initial proposal is to award a $20 million prize for developing a rapid point-of-care diagnostic to help providers identify drug-resistant bacteria.

In addition to spurring R&D, these initiatives will emphasize the importance of preventing resistance by blocking inappropriate use of new antibiotics and by greatly limiting drug use to promote livestock growth.